The Crosstalk Between Amyloid-β, Retina, and Sleep for the Early Diagnosis of Alzheimer's Disease: A Narrative Review

Abstract

Alzheimer's disease (AD) is the most common type of dementia, which is characterised by progressive memory loss and accumulation of hallmark markers amyloid-β (Aβ) and neurofibrillary tangles in the diseased brain. The current gold standard diagnostic methods have limitations of being invasive, costly, and not easily accessible. Thus, there is a need for new avenues, such as imaging the retina for early AD diagnosis. Sleep disruption is symptomatically frequent across preclinical and AD subjects. As circadian activity, such as the sleep-wake cycle, is linked to the retina, analysis of their association may be useful additions for achieving predictive AD diagnosis. In this narrative review, we provide an overview of human retina studies concerning the deposition of Aβ, the role of the retina in sleep-wake cycle, the disruption of sleep in AD, and to gather evidence for the associations between Aβ, the retina, and sleep. Understanding the mechanisms behind the associations between Aβ, retina, and sleep could assist in the interpretation of retinal changes accurately in AD.

Keywords: Alzheimer’s disease; amyloid; dementia; retina; sleep.

Fig. 1

Flowchart of studies included.

Fig. 2

Presentation of deposits in retinal imaging. A) HSI of the retina at 575 nm displaying drusen deposits in the macular region. B) Examples of HSI between 450–580 nm showing deposits of interest outside of the macular region. C) OCT image illustrating drusen deposition in and between the RPE and Bruch’s membrane retinal layers (1). Note: According to literature, the layers of deposition for Aβ are in superior layers, including the RNFL, GCL, and IPL (2) [14], [54]. HSI, hyperspectral imaging; OCT, optical coherence tomography; RPE, retinal pigment epithelium; RNFL, retinal nerve fiber layer; GCL, ganglion cell layer; IPL, inner plexiform layer.

Fig. 3

Proposed mechanism for Aβ in the retina to cause sleep-wake cycle and circadian hormone disruptions. A) Physiological pathway of circadian activity. B) Normal activity of sleep hormone expression in response to light saturation in day and night. C) Changes to sleep-wake patterns in response to AD, Retinal Aβ may disrupt the pathway observed in (A) in AD, thereby causing disruption in sleep quality. D) Circadian hormones effected in AD, where CSF orexin expression is decreased and the attenuation of ghrelin and leptin’s neuroprotective role. Aβ, amyloid-β; AD, Alzheimer’s disease; SCN, suprachiasmatic nucleus.